The Natural History of COPD: Beyond Fletcher and Peto

Abstract

The landmark publication of the "British Postal Worker Study" by Fletcher and colleagues in the 1970s established that chronic obstructive pulmonary disease occurs because smoking exposure in susceptible individuals accelerates the decline of lung function that occurs physiologically with age. In the 40 years since Fletcher et al. published the results of their study, subsequent research has advanced our understanding of chronic obstructive pulmonary disease and its natural history. The current review focuses on areas where the proposal by Fletcher et al. require expansion and/or modification, including: (i) the recognition of the role of exposures other than cigarette smoking (or even in its absence where chronic obstructive pulmonary disease may be related to other conditions such as asthma); (ii) that smoking affects a larger percentage of individuals than suggested by Fletcher et al.; (iii) that the benefits of smoking cessation vary with age/disease severity; (iv) that lung function decline does not accelerate with advancing age; (v) that many can develop chronic obstructive pulmonary disease with "normal" rates of lung function decline if they have abnormal lung growth and, therefore, low lung function at early age; (vi) that the relationship between mucus hypersecretion, exacerbations, and lung function decline is more complex than suggested by Fletcher et al.; and, finally, (vii) Corresponding author: Stephen I. Rennard, srennard@unmc.edu

Natural history of COPD: gaps and opportunities

“…So far, the natural history of COPD has been restricted to the description of changes over time of the degree of airflow limitation as expressed by the forced expiratory volume in 1 s (FEV 1 ) [ 16 ], assuming COPD to be simply a disease that affects only the lungs. Yet, COPD is a complex and heterogeneous disease with different pulmonary and extrapulmonary components that do not necessarily progress in parallel [ 11 , 17 , 18 ], and are not always reflected by FEV 1 [ 19 ].…”

“…None of these trajectories are exclusive. Reproduced from [ 16 ] with permission from the publisher.…”

“…Lung development and growth is a complex and tightly controlled process [ 39 ]. Human lungs develop from the embryonic foregut as buds from the laryngotracheal sulci at 26 days of gestation [ 16 ]. These lung buds undergo dichotomous branching, forming approximately 18 generations of airways over weeks 16–26 of gestation [ 16 ].…”

“…Human lungs develop from the embryonic foregut as buds from the laryngotracheal sulci at 26 days of gestation [ 16 ]. These lung buds undergo dichotomous branching, forming approximately 18 generations of airways over weeks 16–26 of gestation [ 16 ]. Alveolar walls form by septation in a process that continues through childhood [ 16 ].…”

“…These lung buds undergo dichotomous branching, forming approximately 18 generations of airways over weeks 16–26 of gestation [ 16 ]. Alveolar walls form by septation in a process that continues through childhood [ 16 ]. Following formation of alveolar units, the lungs grow in size and surface area as the thorax grows during childhood and adolescence.…”